Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group

R. Ramasubbaiah, S. M. Perkins, J. Schilder, C. Whalen, C. S. Johnson, M. Callahan, T. Jones, G. Sutton, D. Matei

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Objective: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, < 3 prior regimens, normal end-organ function. 3 + 3 dose escalation was used for phase I, sorafenib being tested at 400 mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m 2 to 3.5 mg/m 2 IV weekly. The phase II regimen was sorafenib 400 mg daily and topotecan 3.5 mg/m 2 weekly on days 1, 8, 15 of a 28 days cycle. Results: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. Conclusions: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.

Original languageEnglish (US)
Pages (from-to)499-504
Number of pages6
JournalGynecologic Oncology
Volume123
Issue number3
DOIs
StatePublished - Dec 1 2011

Fingerprint

Topotecan
Ovarian Neoplasms
Platinum
Carcinoma
Hand-Foot Syndrome
Maximum Tolerated Dose
Leukopenia
Neutropenia
Thrombocytopenia
Nausea
Disease-Free Survival
Vomiting
Fatigue
sorafenib
Anemia
Survival Rate

Keywords

  • Clinical trial
  • Ovarian cancer
  • Phase I/II
  • Platinum resistant
  • Sorafenib
  • Topotecan

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group. / Ramasubbaiah, R.; Perkins, S. M.; Schilder, J.; Whalen, C.; Johnson, C. S.; Callahan, M.; Jones, T.; Sutton, G.; Matei, D.

In: Gynecologic Oncology, Vol. 123, No. 3, 01.12.2011, p. 499-504.

Research output: Contribution to journalArticle

Ramasubbaiah, R. ; Perkins, S. M. ; Schilder, J. ; Whalen, C. ; Johnson, C. S. ; Callahan, M. ; Jones, T. ; Sutton, G. ; Matei, D. / Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group. In: Gynecologic Oncology. 2011 ; Vol. 123, No. 3. pp. 499-504.
@article{dfcbcc59c0034e1abc56f28416b7f682,
title = "Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group",
abstract = "Objective: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, < 3 prior regimens, normal end-organ function. 3 + 3 dose escalation was used for phase I, sorafenib being tested at 400 mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m 2 to 3.5 mg/m 2 IV weekly. The phase II regimen was sorafenib 400 mg daily and topotecan 3.5 mg/m 2 weekly on days 1, 8, 15 of a 28 days cycle. Results: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7{\%}), and 14 patients (46.7{\%}) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23{\%}), thrombocytopenia (17{\%}), anemia (10{\%}), fatigue, nausea, vomiting (7{\%} each). One case of grade 3 hand-foot syndrome was recorded. Conclusions: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.",
keywords = "Clinical trial, Ovarian cancer, Phase I/II, Platinum resistant, Sorafenib, Topotecan",
author = "R. Ramasubbaiah and Perkins, {S. M.} and J. Schilder and C. Whalen and Johnson, {C. S.} and M. Callahan and T. Jones and G. Sutton and D. Matei",
year = "2011",
month = "12",
day = "1",
doi = "10.1016/j.ygyno.2011.08.033",
language = "English (US)",
volume = "123",
pages = "499--504",
journal = "Gynecologic Oncology",
issn = "0090-8258",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Sorafenib in combination with weekly topotecan in recurrent ovarian cancer, a phase I/II study of the Hoosier Oncology Group

AU - Ramasubbaiah, R.

AU - Perkins, S. M.

AU - Schilder, J.

AU - Whalen, C.

AU - Johnson, C. S.

AU - Callahan, M.

AU - Jones, T.

AU - Sutton, G.

AU - Matei, D.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Objective: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, < 3 prior regimens, normal end-organ function. 3 + 3 dose escalation was used for phase I, sorafenib being tested at 400 mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m 2 to 3.5 mg/m 2 IV weekly. The phase II regimen was sorafenib 400 mg daily and topotecan 3.5 mg/m 2 weekly on days 1, 8, 15 of a 28 days cycle. Results: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. Conclusions: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.

AB - Objective: This trial determined the efficacy and tolerability of sorafenib and weekly topotecan in patients with platinum-resistant ovarian cancer (OC) or primary peritoneal carcinomatosis (PPC). Methods: Primary endpoints were maximum tolerated dose of sorafenib with weekly topotecan (phase I) and response rate (phase II). Secondary endpoints were progression free survival (PFS), overall survival (OS), toxicity, and rate of clinical benefit. Eligibility included recurrent platinum-resistant OC or PPC, < 3 prior regimens, normal end-organ function. 3 + 3 dose escalation was used for phase I, sorafenib being tested at 400 mg and 800 mg orally daily. Topotecan dose was reduced from 4 mg/m 2 to 3.5 mg/m 2 IV weekly. The phase II regimen was sorafenib 400 mg daily and topotecan 3.5 mg/m 2 weekly on days 1, 8, 15 of a 28 days cycle. Results: 16 patients were enrolled in phase I and 14 patients in phase II. Median age was 52.5 years (range 35-79), 27 patients had OC, and 3 PPC. Median number of cycles administered was 2.5 (0-15). There were 5 partial responses (PR) (16.7%), and 14 patients (46.7%) with stable disease (SD). Four PRs were recorded during phase I and 1 during phase II. One of those PRs occurred in a patient with platinum-sensitive disease. Grade 3/4 toxicities included leukopenia/neutropenia (23%), thrombocytopenia (17%), anemia (10%), fatigue, nausea, vomiting (7% each). One case of grade 3 hand-foot syndrome was recorded. Conclusions: The combination of sorafenib and topotecan causes significant toxicity, precluding administration of full doses and resulting in modest clinical efficacy in platinum resistant OC or PPC.

KW - Clinical trial

KW - Ovarian cancer

KW - Phase I/II

KW - Platinum resistant

KW - Sorafenib

KW - Topotecan

UR - http://www.scopus.com/inward/record.url?scp=81155148279&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=81155148279&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2011.08.033

DO - 10.1016/j.ygyno.2011.08.033

M3 - Article

C2 - 21955480

AN - SCOPUS:81155148279

VL - 123

SP - 499

EP - 504

JO - Gynecologic Oncology

JF - Gynecologic Oncology

SN - 0090-8258

IS - 3

ER -